Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: A randomised crossover placebo-controlled trial

Tropical Medicine and International Health

Volumn 20, Issue 3, 2015, Pages 380-390

  Nakanjako, Damalie ^a   Ssinabulya, Isaac ^a   Nabatanzi, Rose ^a   Bayigga, Lois ^a   Kiragga, Agnes ^a   Joloba, Moses ^a   Kaleebu, Pontiano ^b   Kambugu, Andrew D ^a   Kamya, Moses R ^a   Sekaly, Rafick ^c   Elliott, Alison ^b   Mayanja Kizza, Harriet ^a  

^a MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES   (Uganda)

^b UGANDA VIRUS RESEARCH INSTITUTE   (Uganda)

^c Vaccine and Gene Therapy Institute of Florida   (United States)

Author keywords

Adjunct therapy; Antiretroviral therapy; Atorvastatin; HIV AIDS; Immune activation; Immune recovery

Indexed keywords

ATORVASTATIN; COTRIMOXAZOLE; EFAVIRENZ; LAMIVUDINE; LOW DENSITY LIPOPROTEIN; NEVIRAPINE; STAVUDINE; TENOFOVIR; TRIACYLGLYCEROL; ZIDOVUDINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PYRROLE DERIVATIVE;

FLOW CYTOMETRY; HEALTH SURVEY; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE;

ADULT; ARM PAIN; ARTHRALGIA; ARTICLE; BACKACHE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FLOW CYTOMETRY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; LIVER FUNCTION TEST; LYMPHOCYTE FUNCTION; MALE; MIDDLE AGED; MYALGIA; NECK PAIN; PERIPHERAL BLOOD MONONUCLEAR CELL; RANDOMIZED CONTROLLED TRIAL; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE EXHAUSTION; THORAX PAIN; TREATMENT OUTCOME; UGANDA; COHORT ANALYSIS; DRUG EFFECTS; HIV INFECTIONS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; VIRUS LOAD;

UGANDA;

ADULT; ANTI-HIV AGENTS; ATORVASTATIN CALCIUM; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; COHORT STUDIES; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; HEPTANOIC ACIDS; HIV INFECTIONS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; MALE; MIDDLE AGED; PYRROLES; UGANDA; VIRAL LOAD;

EID: 84922569436     PISSN: 13602276     EISSN: 13653156     Source Type: Journal    
DOI: 10.1111/tmi.12442     Document Type: Article

References (32)

1. Acharjee S & Welty FK (2008) Atorvastatin and cardiovascular risk in the elderly-patient considerations. Clinical Interventions in Aging 3, 299-314.
2. Alluvia Product characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/02/WC500073944.pdf.
3. Archbold RA & Timmis AD (1998) Cholesterol lowering and coronary artery disease: mechanisms of risk reduction. Heart 80, 543-547.
4. Bonham S, Meya DB, Bohjanen PR & Boulware DR (2008) Biomarkers of HIV immune reconstitution inflammatory syndrome. Biomarkers in Medicine 2, 349-361.
5. Borkow G, Weisman Z, Leng Q et al. (2001) Helminths, human immunodeficiency virus and tuberculosis. Scandinavian Journal of Infectious Diseases 33, 568-571.
6. Coban C, Ishii K, Kawai T et al. (2005) Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. The Journal of Experimental Medicine 201, 19-25.
7. Crowe SM, Westhorpe CL, Mukhamedova N, Jaworowski A, Sviridov D & Bukrinsky M (2010) The macrophage: the intersection between HIV infection and atherosclerosis. Journal of Leukocyte Biology 87, 589-598.
8. Ganesan A, Crum-Cianflone N, Higgins J et al. (2011) High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. Journal of Infectious Diseases 203, 756-764.
9. Gerber JG, Rosenkranz SL, Fichtenbaum CJ et al. (2005) Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study. Journal of Acquired Immune Deficiency Syndromes 39, 307-312.
10. Giguere JF & Tremblay MJ (2004) Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. Journal of Virology 78, 12062-12065.
11. Goovaerts O, Jennes W, Massinga-Loembe M et al. (2013) LPS-binding protein and IL-6 mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients. PLoS One 8, e81856.
12. Greenwood J, Steinman L & Zamvil SS (2006) Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nature Reviews Immunology 6, 358-370.
13. Gupta SK, Komarow L, Gulick RM et al. (2009) Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. Journal of Infectious Diseases 200, 614-618.
14. Hunt PW, Martin JN, Sinclair E et al. (2003) T cell activation is associated with lower CD4 + T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. Journal of Infectious Diseases 187, 1534-1543.
15. Hunt PW, Brenchley J, Sinclair E et al. (2008) Relationship between T cell activation and CD4 + T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. Journal of Infectious Diseases 197, 126-133.
16. Hunt PW, Cao HL, Muzoora C et al. (2011) Impact of CD8 + T-cell activation on CD4 + T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy. AIDS 25, 2123-2131.
17. Jain MK & Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nature Reviews Drug Discovery 4, 977-987.
18. Kamya MR, Mayanja-Kizza H, Kambugu A et al. (2007) Academic Alliance for AIDS Care and Prevention in Africa. http://www.ncbi.nlm.nih.gov/pubmed/17693883. Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. J Acquir Immune Defic Syndr. 46(2), 187-93.
19. Kaplan RC, Sinclair E, Landay AL et al. (2011) T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. Journal of Infectious Diseases 203, 452-463.
20. Kwak B, Mulhaupt F, Myit S & Mach F (2000) Statins as a newly recognized type of immunomodulator. Nature Medicine 6, 1399-1402.
21. LaRosa JC, Grundy SM, Waters DD et al. (2005) Intensive lipid lowering with atorvastatin in patients with stable coronary disease. New England Journal of Medicine 352, 1425-1435.
22. Nakanjako D, Kiragga A, Ibrahim F, Castelnuovo B, Kamya MR & Easterbrook PJ (2008) Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on antiretroviral therapy (ART) in sub-Saharan Africa: frequency and clinical significance. AIDS Research and Therapy 5, 23.
23. Nakanjako D, Ssewanyana I, Mayanja-Kizza H et al. (2011) High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infectious Diseases 11, 43.
24. Nakanjako D, Ssewanyana I, Nabatanzi R et al. (2013) Impaired T-cell proliferation among HAART-treated adults with suboptimal CD4 recovery in an African cohort. BMC Immunology 14, 26.
25. Ray KK & Cannon CP (2005) Atorvastatin and cardiovascular protection: a review and comparison of recent clinical trials. Expert Opinion on Pharmacotherapy 6, 915-927.
26. Ray KK, Cannon CP, McCabe CH et al. (2005) Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial. Journal of the American College of Cardiology 46, 1405-1410.
27. del Real G, Jimenez-Baranda S, Mira E et al. (2004) Statins inhibit HIV-1 infection by down-regulating Rho activity. Journal of Experimental Medicine 200, 541-547.
28. Sibbald B & Roberts C (1998) Understanding controlled trials. Crossover trials. BMJ 316, 1719.
29. Ssinabulya I, Kayima J, Longenecker C et al. (2014) Subclinical atherosclerosis among HIV-infected adults attending HIV/AIDS care at two large ambulatory HIV clinics in Uganda. PLoS One 9, e89537.
30. UNAIDS (2012) UNAIDS Report on the global AIDS epidemic. Geneva. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_with_annexes_en.pdf
31. Valentinuzzi M (2004) Review of "Fundamentals of Clinical Trials" by LM. Friedman, CD. and Furberg and DL. DeMets. BioMedical Engineering OnLine 3, 1-2.
32. WHO/UNAIDS/UNICEF (2011) Progress report summary 2011. Geneva. http://www.who.int/hiv/pub/progress_report2011/summary_en.pdf